Systemic Lupus Erythematosus (SLA) Is an autoimmune disorder that predominantly afflicts females in the child-bearing years. The cause(s) of the disorder remain unknown; however, recent progress in understanding the role of T cell dysfunctions in SLE patients has lead to progress in unravelling the molecular pathogenesis of the disease. A generalized failure of the T cell to perform its functions has been characterized in SLE. This impairment in the T cell function contributes to the destructive autoimmune pathogenesis observed in SLE patients. This proposal will investigate one pathway that may contribute to impaired T cell function. We have defined the first disorder of a protein kinase in SLE T cells, characterized by a deficient type I isozyme of protein kinase A (PKA-1). Our working hypothesis is that the RI Beta-subunit protein of PKA-I is deficient due to abnormal synthesis and/or stability of the protein. Our goal is to identify the step at which RI-Beta protein production is altered in SLE T cells. The identification of the cause of RI Beta- subunit deficiency may provide the rationale in the future to apply new therapies in SLE.